| Summary: | <i>Background:</i> This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. <i>Methods</i>: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. <i>Results</i>: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (<i>p</i> = 0.02) and LRFS (<i>p</i> = 0.04). PORT was found to be significantly associated with DFS (<i>p</i> = 0.04) and RFS (<i>p</i> = 0.06). <i>Conclusions</i>: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.
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